Role of mucosal mast cells in visceral hypersensitivity in a rat model of irritable bowel syndrome

The involvement of mucosal mast cells (MMC) in the pathophysiology of irritable bowel syndrome (IBS) is still controversial. We aimed to re-evaluate the role of MMC in visceral hypersensitivity associated with IBS using a rat IBS model that develops the IBS symptom after a subsidence of acetic acid-induced colitis. No significant difference in the number of MMC was observed between normal rat colon and IBS rat colon. (61.7 +/-2.9/mm 2 in normal vs. 88.7 +/-13.3/mm 2 in IBS, p >0.29). However, the degranulation rate of MMC was significantly higher in IBS rat colon (49.5 +/-2.4% in normal vs. 68.8 +/-3.4% in IBS, p >0.05). Pretreatment of a mast cell stabilizer, doxantrazole (5 mg/kg, i.p.), reduced the degranulation rate of MMC and significantly attenuated visceral hypersensitivity to rectal distension in IBS rat, whereas it had no effect on the visceral sensory responses in normal rat. These results suggest that, although the number of MMC is not significantly changed in IBS rat colon, the higher degranulation rate of MMC is responsible for visceral hypersensitivity in this model IBS.

The effect of the application of growth factors on wound contraction : An experimental study in a fibroblast-populated collagen lattice

Many investigators have reported that collagen gel contraction reflects the mechanism of wound contraction. In 1995, Tsai et al. reported that hypertrophic scar-derived fibroblasts in a connective tissue model possessed the greatest contraction potency when compared with those of normal skin and normal oral mucosa-derived CTMs. In this study, we studied the effect of collagen gel contraction by growth factors such as epidermal growth factor, platelet-derived growth factor, transforming growth factor-bata1, and transforming growth factor-bata3, Skin fibroblasts used in this study were obtained from the explant of rat skin culture. Fibroblasts were cultured in Dulbecco's modified Eagle's medium containing 10% fetal bovine serum. Growth factors were added per FPCL in the desired concentrations and we measured the collagen gel diameters in growth factor-treated FPCL on day 1,2,3, and 4 respectively after starting incubation. We examined the effects of EGF, PDGF, TGF-bata1, TGF-bata3 and the effects of combinations of TGF-bata1 + EGF, TGF-bata1 + PDGF, and TGF-bata1 + TGF-bata3 to contract a collagen gel. EGF has little influence on collagen gel contraction. TGF-bata1 and TGF-bata3 increase the collagen contraction. TGF-bata1 enhanced the contractility of collagen gel according to the concentrations. While TGF-bata3 alone had stimulatory contraction effects at low dose, high doses of TGF-bata3 decreased the potency of collagen gel contraction. A combination of TGF-bata1 and EGF minimally decrease TGF-bata1 activity. A combination of TGF-bata1and PDGF had an effect similar to TGF-bata1 activity. A combination of TGF-bata1 and TGF-bata3 decreased TGF-bata1 activity. According to reports that FPCL contraction is equivalent to the process of wound contraction, growth factors which enhance gel contraction may be related to wound contraction and wound healing. TGF-bata1 is reported to enhance scar formation in fetal wound. EGF accelerates wound healing and inhibits the promotion of hypertrophic scar formation. Compared to the effect of collagen gel contraction in this study, the combination of TGF-bata1 and TGF-bata3 that inhibited the promotion of collagen gel contraction are thought to diminish the formation of scar tissue. As well, EGF that has not enhanced collagen gel contraction is thought to diminish the production of scar tissue. We will study the interactive effects of TGF-bata3, EGF and TGF-bata1 on the contraction of collagen gels in the future.